tbuckley/cabot-search huggingface dataset:
Efficacy and safety of anlotinib as first-line treatment and followed by tyrosine kinase inhibitors (TKIs) combined with PD-1 blockades regimen after disease progression for advanced hepatocellular carcinoma (HCC): A real-world exploratory study.
Authors: Qing-Qing Li, Sheng-Li Ma, Lu Zhang, Xian-Qiang Zhang, Xiao-Juan Gao, Yan-Feng Pan
Journal: Journal of Clinical Oncology (2022)

e16146 Background: The prognosis of traditional treatments for patients with HCC was dismal. Small-molecule anti-angiogenic targeted drugs and PD-1 blockades have been shown superior efficacy in advanced HCC. As a novel oral multitarget TKI, anlotinib monotherapy or combined with PD-1 blockades has preliminary efficacy in the treatment of HCC. Consequently, this study was to explore the efficacy and safety of anlotinib as first-line treatment and followed by TKIs combined with PD-1 blockades regimen after disease progression for advanced HCC in real-world. Methods: Patients with advanced HCC with BCLC stage B or C were recruited in this study. Eligible patients received anlotinib (8/10/12mg, po, d1̃14, q3w. Dosage is determined by the clinician) as first-line treatment until disease progression or intolerable toxicity. For those with progressive disease, treatment was administrated with TKIs (anlotinib, apatinib, lenvatinib, or regorafenib) and PD-1 blockades (camrelizumab or sintilimab) until disease progression again or intolerable toxicity. The primary endpoint was PFS (RECIST v 1.1) in the first-line treatment. Secondary endpoints were ORR, DCR, OS and safety. Results: From Feb 2019 to Nov 2021, a total of 62 eligible patients were enrolled. The patients were 55 (38̃78) years of age, including ECOG PS 0 (82.3%) or 1 (17.7%), BCLC stage B (32.3%) or C (67.7%). In the first line treatment, there were 12 CR (19.4%), 17 PR (27.4%), 25 SD (40.3%) and 8 PD (12.9%). Consequently, ORR was 46.8% (95%CI: 34.0%̃59.9%) and DCR was 87.1% (95%CI: 76.1%̃94.3%). At the cut-off date, 41 patients experienced disease progression, the preliminary median PFS was 7.37 months (95%CI: 5.88-8.86), and the median OS was not yet reached. Of the 41 patients with disease progression, 11 patients received TKIs plus PD-1 blockades regimen. There were 3 CR (27.3%), 1 PR (9.1%), 3 SD (27.3%) and 4 PD (36.4%). Therefore, ORR was 36.4% (95%CI: 10.9%̃69.2%) and DCR was 63.6% (95%CI: 30.8%̃89.1%). The safety profile suggested that the most common treatment-emergent adverse events were thrombocytopenia (51.6%), leukopenia (50%), hypertension (46.8%), neutropenia (46.8%), fatigue (43.5%) and hand-foot syndrome (41.9%). The common grade ≥3 treatment-emergent adverse events were hypertension (12.9%), elevated bilirubin (9.7%) and neutropenia (7.9%). Unfortunately, one patient died from gastrointestinal bleeding. Conclusions: The present study indicated that anlotinib as first-line treatment and followed by TKIs combined with PD-1 blockades regimen after disease progression for advanced HCC exhibited potential efficacy and tolerable safety profile in real-world setting. The conclusion should be validated in more pts included subsequently.
How to optimize patient selection before salvage lymph node dissection for nodal recurrent prostate cancer: A novel risk stratification tool
Authors: N. Fossati, J.R. Karnes, A. Heidenreich, A. Kretschmer, A. Buchner, C. Stief, S. Joniau, H. Van Poppel, D. Osmonov, K. Jueneman, S. Shariat, A. Hiester, P. Albers, D. Tilki, M. Graefen, I.S. Gill, D. Pfister, E. Mazzone, G. Gandaglia, A. Stabile, A. Gallina, A. Mottrie, F. Montorsi, A. Briganti
Journal: European Urology (2022)
Cytokine-induced memory-like (CIML) NK cells and association with circulating immune microenvironment.
Authors: Shanshan Xiao, Tongqiang Fan, Qian Wang, Tao Wang
Journal: Journal of Clinical Oncology (2022)

e18042 Background: Cytokine-induced memory-like (CIML) NK cells are attractive for adoptive cell therapeutic approaches due to their key characteristics which include anti-tumor responses, prolonged proliferation and persistence in vivo. Several NK cell subsets have been reported in human and mice, but their heterogeneity and trajectories in human peripheral blood remains poorly characterized. We aimed to evaluate the developmental trajectories and prognosis outcomes of several CIML NK subsets between HPV+ and HPV- HNSC patients. Methods: A publicly available scRNA-seq dataset (only CD45 + PBMC data sets were used) (Kürten et al., 2021) was obtained and stratified by two definitions of CIML NKs: (1) increased granzyme B mRNA expression and (2) preactivated with iterleukin-12 (IL-12), IL-15 and IL-18. Single-cell analysis was performed, followed by sub-clustering of NK populations. Results: 4,794 NK cells from 6 HPV+ and 11 HPV- HNSC patients were analyzed in our study. Expression profiles showed that these NK cells were CD56 dim CD16 + CD57 - NKs. Further investigation showed that these cell populations exhibit a cytokine-induced memory-like phenotype, including increased granzyme B mRNA and preactivated with IL-12, IL-15 and IL-18. Transcriptomic profiles demonstrated that CIML NK cells can be classified into three subsets, including Bl1, Bl2, and Bl3, where Bl1 and Bl3 were found to be consistent with the previous studies, Bl2 was a newly identified NK cluster in this study. Pseudotime analyses suggested that CIML NK cells transitioned from Bl3 (is in cytolytic state) to Bl2, and then (maintains intermediate cell states) to Bl1 (supports cytotoxic activity), regardless of HPV status. There were 20, 60, and 26 Up-regulated genes in Bl, Bl2, and Bl3 in HPV+ patient compared to HPV- patients, respectively. Biocarta pathway analyses showed that NK cell pathway was highly enriched in all NK subsets from HPV+ patients, instead of HPV- patients, indicating a developmental independent characteristic. Survival analyses showed poor prognosis outcomes for high expressed CIML NK signatures in no matter HPV+ or HPV- patients. Conclusions: We investigated CIML NK cells in human peripheral blood and found that Bl1, Bl2, and Bl3 NK clusters showing the developmental patterns of increased cytotoxicity independent of HPV status. The Bl2 is a novel NK cell cluster which presents intermediate cell states. The cluster signatures were correlated with poor clinical outcomes, highlighting its’ potential clinical values for CIML NK-targeted immunotherapies.
Pushing the frontiers of military medical excellence: updates, progress and future needs
Authors: Jun Jie Seah, De-Yun Wang
Journal: Military Medical Research (2022)

Abstract Since its establishment in 2014, Military Medical Research has come a long way in becoming a premier journal for scientific articles from various different specialties, with a special emphasis on topics with military relevance. The field of military medicine may be obscure, and may not be readily encountered by the typical clinician on a day-to-day basis. This journal aims not only to pursue excellence in military research, but also to keep current with the latest advancements on general medical topics from each and every specialty. This editorial serves to recap and synthesize the existing progress, updates and future needs of military medical excellence, discussing foremostly the unique traits of literature published in this journal, and subsequently presenting the discourse regarding wartime and peacetime medicine, the role of the military in a public health emergency, as well as wound healing and organ regeneration. Special attention has been devoted to military topics to shed light on the effects of Chemical, Biological, Radiological and Explosive warfare, environmental medicine and military psychiatry, topics which rarely have a chance to be discussed elsewhere. The interconnectedness between military combat and soldier physical and mental well-being is intricate, and has been distorted by pandemics such as coronavirus disease 2019 (COVID-19). This journal has come a long way since its first article was published, steadily contributing to the existing knowledge pool on general medical topics with a military slant. Only with continuous research and sharing, can we build upon the work of the scientific community, with hopes for the betterment of patient care.
Association of COVID-19 Vaccination During Pregnancy With Incidence of SARS-CoV-2 Infection in Infants
Authors: Ellen Øen Carlsen, Maria C. Magnus, Laura Oakley, Deshayne B. Fell, Margrethe Greve-Isdahl, Jonas Minet Kinge, Siri E. Håberg
Journal: JAMA Internal Medicine (2022)

Pregnant women are recommended to receive COVID-19 vaccination to reduce risk of severe COVID-19. Whether vaccination during pregnancy also provides passive protection to infants after birth remains unclear.To determine whether COVID-19 vaccination in pregnancy was associated with reduced risk of COVID-19 in infants up to age 4 months during COVID-19 pandemic periods dominated by Delta and Omicron variants.This nationwide, register-based cohort study included all live-born infants born in Norway between September 1, 2021, and February 28, 2022.Maternal messenger RNA COVID-19 vaccination during second or third trimester compared with no vaccination before or during pregnancy.The risk of a positive polymerase chain reaction test result for SARS-CoV-2 during an infant's first 4 months of life by maternal vaccination status during pregnancy with either dose 2 or 3 was estimated, as stratified by periods dominated by the Delta variant (between September 1 and December 31, 2021) or Omicron variant (after January 1, 2022, to the end of follow-up on April 4, 2022). A Cox proportional hazard regression was used, adjusting for maternal age, parity, education, maternal country of birth, and county of residence.Of 21 643 live-born infants, 9739 (45.0%) were born to women who received a second or third dose of a COVID-19 vaccine during pregnancy. The first 4 months of life incidence rate of a positive test for SARS-CoV-2 was 5.8 per 10 000 follow-up days. Infants of mothers vaccinated during pregnancy had a lower risk of a positive test compared with infants of unvaccinated mothers and lower risk during the Delta variant-dominated period (incidence rate, 1.2 vs 3.0 per 10 000 follow-up days; adjusted hazard ratio, 0.29; 95% CI, 0.19-0.46) compared with the Omicron period (incidence rate, 7.0 vs 10.9 per 10 000 follow-up days; adjusted hazard ratio, 0.67; 95% CI, 0.57-0.79).The results of this Norwegian population-based cohort study suggested a lower risk of a positive test for SARS-CoV-2 during the first 4 months of life among infants born to mothers who were vaccinated during pregnancy. Maternal COVID-19 vaccination may provide passive protection to young infants, for whom COVID-19 vaccines are currently not available.
Robot-assisted artificial urinary sphincter implantation in female patients: An international multicenter series of 182 patients
Authors: B. Peyronnet, J-N. Cornu, O. Belas, G. Capon, X. Biardeau, P. Lecoanet, L. Castro-Sader, S. Borojeni, R. Hein, J. Hascoet, F. Thibault, F. Dubois, V. Cardot, A. Vidart, A. Descazeaud, G. Fournier, F. Van Der Aa
Journal: European Urology (2022)
Virtual multi-institutional tumor board: Feasibility and physicians acceptance, a GSTU foundation project in Sicily
Authors: V. Serretta, C. Scalici Gesolfo, V. Gebbia, N. Borsellino, D. Di Trapani, G. Ferrera, M. Spada, A. Armenio, M. Lamartina, M.R. Valerio, A. Di Grazia, M. Pennisi, M. Caruso, M. Ruoppolo, M. Barbera, V. Adamo, S. Cimino, A. Firenze, D. Piazza, V. Macchiarella, I. Fazio, M. La Vecchia
Journal: European Urology (2022)
Trend analysis of effect of COVID-19 pandemic on breast cancer staging.
Authors: Li Zhao, Vinit Singh, Farhan Khalid, Margaret Eng, Trishala Meghal
Journal: Journal of Clinical Oncology (2022)

e18682 Background: COVID-19 Pandemic has impacted the diagnosis and treatment of breast cancer and has been shown to increase the late stage cancer at presentation. Most of studies has made year-wise comparison with 2019 for this conclusion. Same studies have also concluded that there was no difference in treatment duration after the diagnosis. Methods: We conducted an IRB-approved retrospective chart review of 505 (255 in 2018 and 250 in 2019) patients diagnosed with Breast Cancer from January 2018 to December 2019 for pre-COVID era and 206 patients diagnosed from March to December 2020 i.e. COVID era. We compared the race, histology, and stage at presentation. Patients from COVID era were compared with newly diagnosed breast cancer in 2018, 2019 patients individually and together. All the above characteristics. were compared between COVID and Pre-COVID era. Continuous variable was compared by T-test and Categorical variable were compared with details were recorded. Descriptive statistics were used in the analysis. Results: Median age of diagnosis for 2018, 2019, and COVID era was 62 (38-83), 59 (37-80) and 64(39-97) respectively. The proportion of white Race during pre-COVID era was 87.52% compared to 89.32% during the COVID era without any significant difference between all 3 years. For Histology, there was significant difference between proportion of histology between 2019 and 2020 (p-value 0.003) whereas no difference between 2018 and 2020 (p-value – 0.21) or combined pre-COVID and COVID era. Incase of staging, significantly more late stage cancer was seen in the COVID era compared to 2019 but there was no significant difference (p-value – 0.225). Same finding was seen between combined pre-COVID and COVID era (p-value - 0.94). Conclusions: Findings from our study suggest that a longer-term trend analysis is required for to find out the accurate impact of COVID-19 pandemic on breast cancer and cancer in general. A population-based study incorporating data from multicenter and multiple year should be done to assess the real effect of COVDI pandemic.[Table: see text]
Multicentre real world long-term outcomes in 2773 primary Non-Muscle Invasive Bladder Cancer (NMIBC) patients managed within the Scottish Bladder Cancer Quality Performance Indicator programme
Authors: P. Mariappan, A. Johnston, M. Trail, S. Hamid, G. Hollins, B.A. Dreyer, S. Ramsey, L. Padovani, R. Garau, J. Guerrero Enriquez, H. Simpson, R. Hasan, C. Sharpe, B.G. Thomas, J. Bhatt, I. Ahmad, G.M. Nandwani, A. Chaudhry, A. Boden, R.S. Khan, G. Maresca, K. Dimitropoulos, C. Graham, D. Hendry
Journal: European Urology (2022)
Eribulin combined with anlotinib for patients with HER2-negative metastatic breast cancer: A single-arm, multicenter, phase II study.
Authors: Yongmei Yin, Xinyu Wu, Yijia Hua, Chunxiao Sun, Yan Liang, Fan Yang, Xiang Huang, Wei Li
Journal: Journal of Clinical Oncology (2022)

e13051 Background: The group of HER2-negative accounts for 70-80% of breast cancer and effective treatments for heavily pretreated patients with HER2-negative metastatic breast cancer are urgently needed. Eribulin mesylate is a non-taxane microtubule dynamics inhibitor with a distinct mode of action which can be used as a chemotherapeutic agent for HER2-negative breast cancer after failure of anthracycline and taxanes treatments. Anlotinib is a novel multitarget tyrosine kinase inhibitor targeting VEGFR, PDGFR, FGFR, and c-Kit. This study aimed to evaluate the efficacy and safety of combined treatment with eribulin and anlotinib in patients with HER2-negative metastatic breast cancer (NCT04624711). Methods: This open-label, single-arm, phase II study enrolled females with HER2-neagtive breast cancer who underwent ≥1 line chemotherapy, including anthracyclines and taxanes, for metastatic breast cancer. Patients with hormone receptor positive breast cancer have underwent ≥1 line endocrine therapy. All patients were treated with Eribulin mesylate (1.4mg/m2, administered intravenously on Days 1 and 8 of each 21 day cycle) and anlotinib (12mg, qd, administered orally on Days 1-14 of each 21 day cycle). The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Results: From November 2020 to February 2022, 25 patients were enrolled in this study. Median follow-up was 3.45 months (95% CI 3.16-5.06). Median PFS was 4.6 months (95% CI 3.55-5.65). Of all the patients whose efficacy could be evaluated (21/25), no patient achieved complete response (CR); 9 (40.91%) and 10 (45.45%) patients got partial response (PR) and stable disease (SD), respectively. ORR was 40.91% and DCR was 86.36%. OS has not reached. The major treatment-related adverse events (incidence≥10%) were neutropenia(48.00%), anemia(37.93%), platelet count decreased (34.48%), fatigue (31.03%), hypoalbuminemia (20.69%), constipation (13.79%), elevated lactate dehydrogenase(13.79%), lymphocyte count decreased (10.34%) and hypertriglyceridemia (10.34%). The most common grade 3/4 adverse events were neutropenia (20.00%). 16.00% (4/25) of patients had dose reductions. Conclusions: The combination of eribulin and anlotinib showed a better treatment response and tolerable toxicity in HER2-negative metastatic breast cancer patients. Further studies enrolling more patients are still needed. Clinical trial information: NCT04624711.
QOL-06. What impact does a posterior fossa tumor in childhood have on motor procedural learning? Group performance depending on radiotherapy status and individual differences on a perceptivo-motor sequence learning task and a motor adaptative task (IMPALA prospective study)
Authors: Eloïse Baudou, Lisa Pollidoro, Jessica Tallet, Jérémy Danna, Jérémie Pariente, Yves Chaix, Anne Laprie
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Procedural memory (PM) is a skill learning system that allows, through training, the automatization of procedures and progressive improvement of performances. The aim of this work was to explore the impact of a posterior fossa tumor (PFT) on PM. We hypothesized that motor adaptation, depending on cortico-cerebellar system, was impaired in PFT survivors treated with and without radiotherapy, and motor sequence learning, depending on cortico-striatal system, was only impaired in PFT treated with radiotherapy. METHODS: We investigated PM in 60 participants from the IMPALA study (NCT04324450) divided into three groups: 39 cured from a PFT in childhood (22 irradiated (PFT+RT group) and 17 non-irradiated (PFT group)) and 21 healthy volunteers (Control group) matched on age, sex and handedness with the PFT+RT group. We used a visuo-motor learning test, the Serial Reaction Time task (SRTT) and a motor adaptation task (MAT) of backwards handwriting. ANOVA and mixed models were used for statistical analysis. RESULTS: SRTT performance analysis showed an effect of Block in specific sequence learning (F(1)48.70,p&amp;lt;0.001) with a preserved specific learning in the three groups. However individual differences were observed with 7/22 patients in PFT+RT group and 4/17 in PFT group who did not have specific learning. MAT performance analysis showed an effect of interaction between Orientation (forward or backward) and Group for speed (F(2)15.58,p&amp;lt;0.001), linearity (F(2)8.39,p&amp;lt;0.001) and amplitude standard deviation (F(2)15.70,p&amp;lt;0.001) traducing an impairment both in PFT+RT and PFT groups, more marked in the PFT+RT group. CONCLUSION: We showed impairment, predominantly on motor adaptation but also, at individual level, in motor sequence learning whose origin requires additional work. This study brings new insights on the long-term impact of a PFT in childhood on a rarely investigated part of memory that is PM.
ANKRD36 mutation as a negative predictor for melanoma immunotherapy.
Authors: Bing Chen, Shizhou Guo, Xiaodan Xing, Qianru He, Qin Zhang, Qianqian Duan, Tingting Sun, Chuang Qi
Journal: Journal of Clinical Oncology (2022)

e21517 Background: Melanoma is one of the most aggressive and immunogenic tumors. Current immunotherapies using immune checkpoint inhibitors such as CTLA4 and PD1 to stimulate T cell-mediated tumor killing significantly improved the overall survival of patients with metastatic melanoma. However, the clinical predictors of response to these therapies are still not fully characterized. Previous studies have shown that the high gene expression of Ankyrin repeat domain 36 (ANKRD36) can lead to the occurrence and poor prognosis of colon cancer and kidney cancer. In this study, we aimed to explore the role of ANKRD36 mutation in the prognosis of melanoma immune checkpoint inhibitors (ICIs). Methods: Public data of patients treated with ICIs(ipilimumab) from Van Allen (n = 110) cohort were obtained and analyzed. In survival analysis, Kaplan-Meier curves were compared by log-rank test, and the hazard ratio (HR) was determined through a multivariable Cox regression model. The potential mechanism was subsequently explored through RNA expression data from The Cancer Genome Atlas (TCGA). Results: The frequency of ANKRD36 mutation in the Van Allen cohort and TCGA cohort was 7.2% (8 in 110) and 1.56% (7 in 448) respectively. We further analyzed the Kaplan Meier curve and multiple Cox regression model of the Allen cohort and found that the survival of the mutant type in immunotherapy was significantly shorter than that of the wild-type group (PFS: HR = 3.09 [95% CI: 1.47, 6.51], p = 0.002; OS: HR = 2.33 [95% CI: 1.12, 4.86], p = 0.02). Both mutant type and tumor metastasis would have negative effects on immunotherapy(PFS: HR = 3.66 [95% CI: 1.71, 7.85], p &lt; 0.001***; OS: HR = 3.16 [95% CI: 1.47, 6.82], p = 0.003**). Analysis of the transcriptome data from the TCGA database found that resting CD4 memory T cells is highly expressed in ANKRD36 mutant patients (p = 0.032), which may indicate that the patient's immune system did not activate the anti-tumor immune mechanism. Conclusions: In our study, the frequency of ANKRD36 mutations was investigated in clinical and TCGA cohorts, which may provide useful information for guiding patient treatment. ANKRD36 mutation may be a negative predictor of ICIs in patients with melanoma and play a role in prognosis.
Activity and safety of topical pimecrolimus in patients with early stage mycosis fungoides (PimTo-MF): a single-arm, multicentre, phase 2 trial
Authors: Pablo L Ortiz-Romero, Lidia Maroñas Jiménez, Cristina Muniesa, Teresa Estrach, Octavio Servitje, Ricardo Fernández-de-Misa, Fernando Gallardo, Onofre Sanmartín, Erica Riveiro-Falkenbach, Nuria García-Díaz, Rosa Vega, David Lora, Concepción Postigo, Blanca Jiménez, Margarita Sánchez-Beato, José Pedro Vaqué, José Luis Rodríguez Peralto, Agustín Gómez de la Cámara, Javier de la Cruz, Miguel Ángel Piris Pinilla
Journal: The Lancet Haematology (2022)